Addition and condensation reactions 43
1.10.3 Mannich reaction
R 2 NCH 2 + H 2 O (Eq. 1.4)
R 2 NCH 2 C(NO 2 ) 3 (Eq. 1.5)
R 2 NCH 2 OH
R 2 NCH 2
R 2 NH + CH 2 O
+ C(NO 2 ) 3
Figure 1.73
The Mannich reaction is an excellent route to polynitroaliphatic amines and their deriva-
tives.β-Nitroalkylamines are formed from the reaction of an amine and aldehyde in the
presence of a nitroalkane (Equations 1.4 and 1.5).^282 −^296 A large number of these reactions
use nitroform,^285 −^287 fluorodinitromethane,^37 ,^256 ,^261 ,^262 or their methylol derivatives, 2,2,2-
trinitroethanol^284 ,^291 and 2-fluoro-2,2-dinitroethanol,^37 ,^256 ,^261 ,^262 to synthesize the correspond-
ing trinitromethyl and fluorodinitromethyl derivatives respectively.
Primary and secondary nitroalkanes, dinitromethane,^282 and terminalgem-dinitroaliphatic
compounds like 1,1-dinitroethane,^284 ,^288 all contain acidic protons and have been used to
generate Mannich products. Formaldehyde is commonly used in these reactions although the
use of other aliphatic aldehydes has been reported.^282 The nitroalkane component is frequently
generatedin situfrom its methylol derivative, a reaction which also generates formaldehyde.
Ammonia,^282 ,^289 −^291 aliphatic amines,^282 −^289 hydrazine,^288 ,^289 and even urea^291 have been used
as the amine component of Mannich reactions.
C
O
H 2 N NH 2
NO 2
C
NO 2
2 N CH 2 OHO
NO 2
2 NCHCO 2 NHCONHCH 2
NO 2
CNO 2
NO 2
NO 2
159
+
82 %
160
(DiTeU)
Figure 1.74
HC(NO 2 ) 3 HN
CH 2 C(NO 2 ) 3
or (CH 2 ) 6 N 4 , 60 –70 % CH 2 C(NO 2 ) 3
NH 3 , CH 2 O, 90 %
161
112
Figure 1.75
The powerful explosive, bis(2,2,2-trinitroethyl)urea (160) (DiTeU), is synthesized from the
reaction of 2,2,2-trinitroethanol (159) with urea, or from the direct reaction of nitroform with
formaldehyde and urea.^291 Bis(2,2,2-trinitroethyl)amine (161) has been synthesized from the
reaction of 2,2,2-trinitroethanol with ammonia and also from the reaction of nitroform (112)
with formaldehyde and ammonia, or hexamine.^291 ,^296
NH 2 NH 2
AcOH (aq)
NO 2
C
NO 2
3 CH 2 OHCH
NO 2
C
NO 2
CH 3 CH 2 NHNHCH 2 C
NO 2
NO 2
CH 3
60 °C, 73 %
+
25 162
Figure 1.76